Unknown

Dataset Information

0

A protecting group-free synthesis of deazathiamine: a step toward inhibitor design.


ABSTRACT: The discovery of 3-deazathiamine diphosphate (deazaThDP) as a potent inhibitor analog of the cofactor thiamine diphosphate (ThDP) has highlighted the need for an efficient and scalable synthesis of deazaThDP. Such a method would facilitate development of analogs with the ability to inhibit individual ThDP-dependent enzymes selectively. Toward the goal of developing selective inhibitors of the mycobacterial enzyme 2-hydroxy-3-oxoadipate synthase (HOAS), we report an improved synthesis of deazaThDP without use of protecting groups. Tribromo-3-methylthiophene served as a versatile starting material whose selective functionalization permitted access to deazaThDP in five steps, with potential to make other analogs accessible in substantial amounts.

SUBMITTER: Zhao H 

PROVIDER: S-EPMC2957563 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

A protecting group-free synthesis of deazathiamine: a step toward inhibitor design.

Zhao Hong H   de Carvalho Luiz Pedro S LP   Nathan Carl C   Ouerfelli Ouathek O  

Bioorganic & medicinal chemistry letters 20100916 22


The discovery of 3-deazathiamine diphosphate (deazaThDP) as a potent inhibitor analog of the cofactor thiamine diphosphate (ThDP) has highlighted the need for an efficient and scalable synthesis of deazaThDP. Such a method would facilitate development of analogs with the ability to inhibit individual ThDP-dependent enzymes selectively. Toward the goal of developing selective inhibitors of the mycobacterial enzyme 2-hydroxy-3-oxoadipate synthase (HOAS), we report an improved synthesis of deazaThD  ...[more]

Similar Datasets

| S-EPMC8252117 | biostudies-literature
| S-EPMC6155830 | biostudies-other
| S-EPMC5496566 | biostudies-other
| S-EPMC3869274 | biostudies-literature
| S-EPMC5486986 | biostudies-literature
| S-EPMC8495876 | biostudies-literature
| S-EPMC5088714 | biostudies-literature
| S-EPMC3762507 | biostudies-literature
| S-EPMC3809131 | biostudies-literature
| S-EPMC3071631 | biostudies-literature